First-line Treatment of Ewing Tumours With Primary Extrapulmonary Dissemination in Patients From 2 to 50 Years (CombinaiR3) (CombinaiR3)

November 18, 2025 updated by: Institut Curie

CombinaiR3 - First-line Treatment of Ewing Tumours With Primary Extrapulmonary Dissemination in Patients From 2 to 50 Years

Ewing's sarcoma and related tumours (ESFT) are rare tumours, with a peak incidence in the second decade of life. They start most often from bone, and are characterized by a specific translocation involving the so-called EWS gene. In one patient out of three, the staging procedures detect metastatic tumours at the diagnosis, most commonly in lungs, bones, and bone marrow.

ESFT treatment strategy is multidisciplinary, combining primary chemotherapy, a local treatment, and consolidation chemotherapy.

The primary metastatic dissemination is the most important prognostic factor, as the survival rate is around 70-75% for localized tumours, in contrast with less than 50% for patients with primary metastatic disease.

Among primary metastatic patients, bone involvement and / or bone marrow strike markedly the prognosis of these patients. While the long-term survival of patients with isolated pleural pulmonary metastases is approximately 50%, whereas it is only from 0 to 25% in patients with bone marrow involvement.

In 1999, the Intergroup EURO EWING built a new study protocol for patients with Ewing tumours. For the patients with primary extrapulmonary metastatic Ewing tumours (R3 patients), the protocol proposed a heavy induction chemotherapy, in order to propose a consolidation with high dose chemotherapy to a higher rate of patients. The high-dose Busulfan Melphalan chemotherapy (BuMel) was based on Busulfan (600 mg/m²) and Melphalan (140 mg/m²), with autologous peripheral blood stem cell (PBSC) support.

Of note, for the full population of patients with metastatic disease, the 3-year EFS rate was 27% (SD 3%), and the OS rate was 34% (SD 4%), with a median follow-up of 3.9 years after diagnosis, and a median survival time of 1.6 years.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Ewing's sarcoma and related tumours (ESFT) are rare tumours, with a peak incidence in the second decade of life. They start most often from bone, and are characterized by a specific translocation involving the so-called EWS gene. The gene rearrangement results in the production of a transcription factor, in the majority EWS-FLI1 transcription.

In one patient out of three, the staging procedures detect metastatic tumours at the diagnosis; metastases involve most commonly lungs, bones, and bone marrow.

Therefore, in addition to local imaging, the initial extension assessment of any Ewing tumour includes at least a chest CT scan, and a bone marrow extensive evaluation, comprising bone marrow punctures into several different sectors, bone marrow biopsies, and a bone imaging evaluation. The FDG-PET scan is more sensible than bone scan and conventional imaging as MRI in detection of bone metastases. It is more and more widely used in the bone metastasis search in Ewing tumours and seems useful to complement the search of extra-osseous metastases (outside the lungs), including that of bone marrow metastases. The full-body MRI is still under evaluation for the disease extension evaluation.

ESFT treatment strategy is multidisciplinary, combining primary chemotherapy, a local treatment, and consolidation chemotherapy. The local treatment may combine surgery and / or radiotherapy, according to the tumour site and size, and to the tumour response. ESFT chemotherapy is based on alkylating agents (ifosfamide and / or cyclophosphamide), etoposide, anthracyclines, vincristine, and actinomycin.

The primary metastatic dissemination is the most important prognostic factor, as the survival rate is around 70-75% for localized tumours, in contrast with less than 50% for patients with primary metastatic disease. Among primary metastatic patients, bone involvement and / or bone marrow strike markedly the prognosis of these patients. While the long-term survival of patients with isolated pleural pulmonary metastases is approximately 50%, whereas it is only from 0 to 25% in patients with bone marrow involvement.

In 1999, the Intergroup EURO EWING built a new study protocol for patients with Ewing tumours, localized or metastatic and below 50 years of age. For the patients with primary extrapulmonary metastatic Ewing tumours (R3 patients), the protocol proposed a heavy induction chemotherapy, in order to propose a consolidation with high dose chemotherapy to a higher rate of patients. The high-dose BuMel chemotherapy was based on Busulfan (600 mg/m²) and Melphalan (140 mg/m²), with autologous peripheral blood stem cell (PBSC) support.

The study enrolled 281 patients with primary dissemination and skeletal metastases, with or without bone marrow involvement and with or without additional pulmonary metastases or metastases to other sites. In contrast to the distribution in the entire group of patients with Ewing tumours, the primary site in this subgroup was extremity in only 31% patients, pelvis/abdomen in 45%, and axial/other in 24% patients. The overall survival at 3 years was 28% (SD 4%) in the group with primary tumour in the abdomen or pelvis, versus 39% (SD 6%) for each of the two other groups. Of note, for the full population of patients with metastatic disease, the 3-year EFS rate was 27% (SD 3%), and the OS rate was 34% (SD 4%), with a median follow-up of 3.9 years after diagnosis, and a median survival time of 1.6 years.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
45

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Bordeaux, France, 33076
        • Bordeaux CHU
      • Grenoble, France, 38043
        • Chu Grenoble Alpes
      • Lille, France, 59000
        • LILLE Centre Oscar Lambret
      • Lyon, France, 69000
        • LYON Centre Léon Bérard
      • Marseille, France, 13000
        • Marseille Chu
      • Montpellier, France, 34295
        • CHRU Montpellier - Hôpital A. de Villeneuve
      • Nantes, France, 44000
        • Nantes CHU
      • Paris, France, 75005
        • PARIS Institut Curie
      • Paris, France, 75012
        • PARIS Trousseau
      • Rennes, France, 35056
        • CHU Hopital Sud
      • Strasbourg, France, 67098
        • Strasbourg Chu
      • Toulouse, France, 31059
        • Toulouse Chu
      • Toulouse, France, 31059
        • TOULOUSE Institut Claudius Regaud
      • Vandœuvre-lès-Nancy, France, 54519
        • NANCY Institut de Cancérologie de Lorraine
      • Vandœuvre-lès-Nancy, France, 54511
        • Nancy Chu
      • Villejuif, France, 94805
        • VILLEJUIF Institut Gustave Roussy
    • Saint Denis
      • La Réunion, Saint Denis, France, 97400
        • Chr Felix Guyon

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 years to 50 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. - Ewing tumour histologically or cytologically confirmed, harboring a specific transcript, and with extrapulmonary metastases (including nodal extension) - histology and FISH results must be consistent, specific transcript can be obtained after inclusions.
  2. - Ewing tumour not previously treated.
  3. - Age between 2 and 50 years.
  4. - Measurable disease by cross sectional imaging (RECIST 1.1) or evaluable disease with functional metabolic, positron emission tomography scanner (PET SCAN) or other methods (e.g., cytology/histology).
  5. - General status compatible with the study treatments (LANSKY score ≥ 50%, or Karnofsky ≥ 50%, or Eastern Cooperative Oncology Group (ECOG) ≤ 2).

  6. - Adequate bone marrow function (not applicable in case of bone marrow disease).

    • Platelets ≥ 100 x 109 /L
    • Absolute Neutrophil Count (ANC) ≥ 1 x 109 /L
    • Hemoglobin ≥ 8g /dL.

  7. - Adequate liver function :

    • Aspartate Aminotransferase (AST) and Alanine Transferase (ALT) ≤ 5 x Upper Limit Normal (ULN)
    • Total Bilirubin ≤ 2 Upper Limit Normal (ULN). If total bilirubin > 2xULN, Bilirubin Conjugated Fraction (BCF) ≤ 2 x ULN
  8. - No absolute contra-indication of Busulfan-Melphalan if radiotherapy of the primary tumour is necessary with specific attention to patient with primary spinal tumor.

  9. - Adequate cardiac and renal functions:

    • Creatinine < 1.5 of normal for age or clearance > 60 ml/min/1.73 m²;
    • Left Ventricular Ejection Fraction (LVEF) > 50% and/or shortening fraction > 28%.
  10. - No underlying disease contra-indicating the study treatments.
  11. - Patient likely compliant with the recommended study medical monitoring during and after treatments.
  12. - Patients of childbearing potential must agree to use adequate contraception for the duration of study treatments and up to 12 months for women and 6 months for men following completion of therapy.
  13. - Females of childbearing potential must have a negative serum β-human chorionic gonadotropin (HCG) pregnancy test within 10 days prior study inclusion, and/or urine pregnancy test within 48 hours before the first administration of the study treatment.
  14. - Patients covered by a health insurance system.
  15. - Patient, or patient's legal representative, informed and having signed the informed consent.

Exclusion Criteria:

  1. - Age below 2 or greater than 50 years.
  2. - Ewing tumour localized, or solely with pleural and/or lung metastases.
  3. - Concomitant disease, particularly infectious disease, likely to interfere with patient's treatment.
  4. - History of cancer, according to investigator's judgment.
  5. - Life expectancy < 2 months.
  6. - Patient already included in another clinical trial with an investigational drug.
  7. - Pregnant or breastfeeding patient.
  8. - Person deprived of liberty or under guardianship.
  9. - Patient likely unable to comply with the study medical monitoring for geographical, social or psychological reasons.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: VDC - IE x2 & Surgery

Patients in Arm A receive

  • VDC-IE x2: Intensified induction phase:

    • 4 cycles of VDC (Vincristine Doxorubicine Cyclophosphamide) association alternative with 4 cycles of IE (Ifosfamide-Etoposide) association if "good response" after the 4th treatment, followed by:
    • 4 cycles of VDC (Vincristine-Doxorubicine-Cyclophosphamide) association alternative with 4 cycles of IE (Ifosfamide-Etoposide) association
  • Consolidation BuMel High dose chemotherapy (Busulfan Melphalan) followed by Peripheral Blood Stem Cell Infusion
  • Local treatment by surgery of primary tumour/metastatic sites (outside pulmonary sites): indicated before of after consolidation phase (BuMel) among multidisciplinary decision. Radiotherapy can be added

  • Maintenance phase

    • 1st year : VC (Vincristine Cyclophosphamide) association
    • 2nd year : Cyclophosphamide po 25 mg/m²
Drug: VDC-IE x2

Week 1, 5, 9 and week 13:

  • Vincristine, IV, D1, 1.5mg/m²
  • Doxorubicine, IV, D1-D2, 37.5mg/m²
  • Cyclophosphamide, IV, D1, 1.2g/m²

Week 3, 7, 11 and week 15:

  • Ifosfamide, IV, D15 to D19, 1.8g/m²/d
  • Etoposide, IV, D15 to D19, 100mg/m²/d
Other Names:
  • Intensified Induction VDC-IE x2
Drug: Consolidation BuMel

After induction phase and local treatment (surgery and/or radiotherapy) and before PBSC:

  • Busulfan, IV, D-5 to D-2, dosa according to the weight
  • Melphalan, IV, D-1, 140 mg/m²

Peripheral Blood Stem Cell infusion:

- PBSC infusion, D0, at least 3.10^6 CD34/kg

Other Names:
  • High dose Consolidation chemotherapy
Drug: Maintenance

* 1st year : VC

  • Vinblastine, IV, 3mg/m², once a week (except during radiotherapy: 1mg/m², 3 times a week)
  • Cyclophosphamide, PO, 25mg/m² continuously
Other Names:
  • 2 years maintenance
Procedure: Local treatment by surgery
Surgical excision of whole site of the primary tumour and metastatic sites (outside pulmonary sites) can take place before or after the high dose consolidation chemotherapy. Radiotherapy can be added
Other Names:
  • Surgery of primary tumour/metastatic sites
Radiation: Local treatment by radiotherapy
Radiotherapy of whole site of the primary tumour and metastatic sites (outside pulmonary sites) can take place before or after the high dose consolidation chemotherapy
Other Names:
  • Radiotherapy of primary tumour/metastatic sites
Other: VDC - IE & TEMIRI & Surgery

Patients in Arm B receive

  • VDC-IE & TEMIRI: Intensified induction phase:

    • 4 cycles of VDC (Vincristine-Doxorubicine-Cyclophosphamide) association alternative with 4 cycles of IE (Ifosfamide-Etoposide) association if "poor response" after the 4th treatment, followed by:
    • 4 cycles of TEMIRI (Temozolomide-Irinotecan) association
  • Local treatment by surgery of primary tumour/metastatic sites (outside pulmonary sites): indicated before of after consolidation phase (BuMel) among multidisciplinary decision. Radiotherapy can be added
  • Consolidation BuMel High dose chemotherapy (Busulfan-Melphalan) followed by Peripheral Blood Stem Cell Infusion

  • Maintenance phase

    • 1st year : VC (Vincristine Cyclophosphamide) association
    • 2nd year : Cyclophosphamide po 25 mg/m²
Drug: Consolidation BuMel

After induction phase and local treatment (surgery and/or radiotherapy) and before PBSC:

  • Busulfan, IV, D-5 to D-2, dosa according to the weight
  • Melphalan, IV, D-1, 140 mg/m²

Peripheral Blood Stem Cell infusion:

- PBSC infusion, D0, at least 3.10^6 CD34/kg

Other Names:
  • High dose Consolidation chemotherapy
Drug: Maintenance

* 1st year : VC

  • Vinblastine, IV, 3mg/m², once a week (except during radiotherapy: 1mg/m², 3 times a week)
  • Cyclophosphamide, PO, 25mg/m² continuously
Other Names:
  • 2 years maintenance
Procedure: Local treatment by surgery
Surgical excision of whole site of the primary tumour and metastatic sites (outside pulmonary sites) can take place before or after the high dose consolidation chemotherapy. Radiotherapy can be added
Other Names:
  • Surgery of primary tumour/metastatic sites
Radiation: Local treatment by radiotherapy
Radiotherapy of whole site of the primary tumour and metastatic sites (outside pulmonary sites) can take place before or after the high dose consolidation chemotherapy
Other Names:
  • Radiotherapy of primary tumour/metastatic sites
Drug: VDC-IE

Week 1 and week 5:

  • Vincristine, IV, D1, 1.5mg/m²
  • Doxorubicine, IV, D1-D2, 37.5mg/m²
  • Cyclophosphamide, IV, D1, 1.2g/m²

Week 3, and week 7:

  • Ifosfamide, IV, D15 to D19, 1.8g/m²/d
  • Etoposide, IV, D15 to D19, 100mg/m²/d
Other Names:
  • Intensified Induction VDC-IE
Drug: TEMIRI

Week 9, 12, 15 and week 18:

  • Temozolomide, PO, D1 to D5, 150mg/m²/d
  • Irinotecan, IV, D1 to D5, 50mg/m²/d
Other Names:
  • Intensified Induction TEMIRI
Other: VDC - IE x2 & Radiotherapy

Patients in Arm C receive

  • VDC-IE x2: Intensified induction phase:

    • 4 cycles of VDC (Vincristine-Doxorubicine-Cyclophosphamide) association alternative with 4 cycles of IE (Ifosfamide-Etoposide) association if "good response" after the 4th treatment, followed by:
    • 4 cycles of VDC (Vincristine-Doxorubicine-Cyclophosphamide) association alternative with 4 cycles of IE (Ifosfamide-Etoposide) association
  • Consolidation BuMel High dose chemotherapy (Busulfan-Melphalan) followed by Peripheral Blood Stem Cell Infusion
  • Local treatment by radiotherapy of primary tumour/metastatic sites (outside pulmonary sites): indicated before of after consolidation phase (BuMel) among multidisciplinary decision.
  • Consolidation BuMel High dose chemotherapy (Busulfan-Melphalan) followed by Peripheral Blood Stem Cell Infusion

  • Maintenance phase

    • 1st year : VC (Vincristine Cyclophosphamide) association
    • 2nd year : Cyclophosphamide po 25 mg/m²
Drug: VDC-IE x2

Week 1, 5, 9 and week 13:

  • Vincristine, IV, D1, 1.5mg/m²
  • Doxorubicine, IV, D1-D2, 37.5mg/m²
  • Cyclophosphamide, IV, D1, 1.2g/m²

Week 3, 7, 11 and week 15:

  • Ifosfamide, IV, D15 to D19, 1.8g/m²/d
  • Etoposide, IV, D15 to D19, 100mg/m²/d
Other Names:
  • Intensified Induction VDC-IE x2
Drug: Consolidation BuMel

After induction phase and local treatment (surgery and/or radiotherapy) and before PBSC:

  • Busulfan, IV, D-5 to D-2, dosa according to the weight
  • Melphalan, IV, D-1, 140 mg/m²

Peripheral Blood Stem Cell infusion:

- PBSC infusion, D0, at least 3.10^6 CD34/kg

Other Names:
  • High dose Consolidation chemotherapy
Drug: Maintenance

* 1st year : VC

  • Vinblastine, IV, 3mg/m², once a week (except during radiotherapy: 1mg/m², 3 times a week)
  • Cyclophosphamide, PO, 25mg/m² continuously
Other Names:
  • 2 years maintenance
Radiation: Local treatment by radiotherapy
Radiotherapy of whole site of the primary tumour and metastatic sites (outside pulmonary sites) can take place before or after the high dose consolidation chemotherapy
Other Names:
  • Radiotherapy of primary tumour/metastatic sites
Other: VDC - IE & TEMIRI & Radiotherapy

Patients in Arm D receive

  • VDC-IE & TEMIRI: Intensified induction phase:

    • 4 cycles of VDC (Vincristine-Doxorubicine-Cyclophosphamide) association alternative with 4 cycles of IE (Ifosfamide-Etoposide) association if "poor response" after the 4th treatment, followed by:
    • 4 cycles of TEMIRI (Temozolomide-Irinotecan) association
  • Local treatment by radiotherapy of primary tumour/metastatic sites (outside pulmonary sites): indicated before of after consolidation phase (BuMel) among multidisciplinary decision.
  • Consolidation BuMel High dose chemotherapy (Busulfan-Melphalan) followed by Peripheral Blood Stem Cell Infusion

  • Maintenance phase

    • 1st year : VC (Vincristine Cyclophosphamide) association
    • 2nd year : Cyclophosphamide po 25 mg/m²
Drug: Consolidation BuMel

After induction phase and local treatment (surgery and/or radiotherapy) and before PBSC:

  • Busulfan, IV, D-5 to D-2, dosa according to the weight
  • Melphalan, IV, D-1, 140 mg/m²

Peripheral Blood Stem Cell infusion:

- PBSC infusion, D0, at least 3.10^6 CD34/kg

Other Names:
  • High dose Consolidation chemotherapy
Drug: Maintenance

* 1st year : VC

  • Vinblastine, IV, 3mg/m², once a week (except during radiotherapy: 1mg/m², 3 times a week)
  • Cyclophosphamide, PO, 25mg/m² continuously
Other Names:
  • 2 years maintenance
Radiation: Local treatment by radiotherapy
Radiotherapy of whole site of the primary tumour and metastatic sites (outside pulmonary sites) can take place before or after the high dose consolidation chemotherapy
Other Names:
  • Radiotherapy of primary tumour/metastatic sites
Drug: VDC-IE

Week 1 and week 5:

  • Vincristine, IV, D1, 1.5mg/m²
  • Doxorubicine, IV, D1-D2, 37.5mg/m²
  • Cyclophosphamide, IV, D1, 1.2g/m²

Week 3, and week 7:

  • Ifosfamide, IV, D15 to D19, 1.8g/m²/d
  • Etoposide, IV, D15 to D19, 100mg/m²/d
Other Names:
  • Intensified Induction VDC-IE
Drug: TEMIRI

Week 9, 12, 15 and week 18:

  • Temozolomide, PO, D1 to D5, 150mg/m²/d
  • Irinotecan, IV, D1 to D5, 50mg/m²/d
Other Names:
  • Intensified Induction TEMIRI

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Anti-tumour effect of the treatment strategy assessed by the number of patients event-free survival (EFS) at 18 months
Time Frame: 18 months after inclusion of the last patient
EFS is defined as the time from inclusion date to the first documentation of progression, distant disease, second cancer or death (or last news for patients free of event). The event free survival is estimated by Kaplan-Meier method.
18 months after inclusion of the last patient

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Anti-tumour effect of the dose-intensified induction chemotherapy assessed by the response rate of patients
Time Frame: week 19-20 = Response Evaluation 2 (RE2)
Number of patients with complete response (CR) / partial response (PR) eligible for consolidation phase
week 19-20 = Response Evaluation 2 (RE2)
Anti-tumour effect of the dose-intensified induction chemotherapy assessed by the number of patients eligible for consolidation phase
Time Frame: week 19-20 = RE2

Number of patients eligible for consolidation phase have good response after induction phase :

  • complete remission on primary tumour and on metastatic sites or

  • very good disease response defined by:

    • complete or partial response according to RECIST 1.1 criteria on primary lesion
    • complete or very good partial response (> 90 %) in case of RECIST 1.1 criteria on metastatic sites AND
    • complete metabolic response in case of metastatic visceral and/or bone/bone marrow lesions, or very good partial response according to investigator's judgment AND
    • in case of bone marrow involvement, bone marrow free of disease on at least one biopsy and two punctures at different sites at RE1 (evaluation after 4 cycles VDC-IE), RE2 (evaluation after 2x4 cycles VDC-IE or 4 cycles VDC-IE+4 cycles TEMIRI), or at the latest RE3 evaluation (evaluation after local treatment).
week 19-20 = RE2
Overall survival (OS) is assessed by the number of patients still alive at the end of the three years of treatment
Time Frame: 3 years = Response Evaluation End-Of-Treatment (EOT RE)
The overall survival (OS) is estimated by Kaplan-Meier method.
3 years = Response Evaluation End-Of-Treatment (EOT RE)
3-years event-free survival (EFS) is assessed by the number of patients without any event at the end of treatment phase
Time Frame: 3 years = EOT RE
EFS is defined as the time from inclusion date to the first documentation of progression, distant disease, second cancer or death (or last news for patients free of event). The event free survival is estimated by Kaplan-Meier method.
3 years = EOT RE
Number of patients with treatment-related adverse events as assessed by CTCAE v4.03
Time Frame: week 19-20 = RE2 ; week 27-28 = Response Evaluation 3 (RE3); 3 years = EOT RE
Number of patients with treatment-related adverse events using the NCI CTCAE version 4.03 to graduate the severity of adverse events
week 19-20 = RE2 ; week 27-28 = Response Evaluation 3 (RE3); 3 years = EOT RE
Number of patients with treatment-related toxicities on laboratory data as assessed by CTCAE v4.03 of the different phases of treatment
Time Frame: week 19-20 = RE2 ; week 27-28 = RE3; 3 years = EOT RE
Number of patients with treatment-related toxicities on laboratory data using the NCI CTCAE version 4.03 to graduate the severity of toxicities
week 19-20 = RE2 ; week 27-28 = RE3; 3 years = EOT RE
18F-FDG PET evaluation efficacy assessed by primary tumour uptake
Time Frame: study inclusion, after week 8 (RE1), after week18-19 (if VDC-IE) or week19-20 (if TEMIRI)=RE2, after local treatment ≤week30 (RE3), from week31 (=RE4), 3 years = EOT RE
Efficacy assessed by primary tumour uptake (Standardized Uptake Value max at 18F-FDG PET)
study inclusion, after week 8 (RE1), after week18-19 (if VDC-IE) or week19-20 (if TEMIRI)=RE2, after local treatment ≤week30 (RE3), from week31 (=RE4), 3 years = EOT RE
18F-FDG PET evaluation efficacy assessed by metabolic tumour volume (MTV)
Time Frame: study inclusion, after week 8 (RE1), after week18-19 (if VDC-IE) or week19-20 (if TEMIRI)=RE2, after local treatment ≤week30 (RE3), from week31 (=RE4), 3 years = EOT RE
Efficacy assessed by metabolic tumour volume (MTV at 18F-FDG PET)
study inclusion, after week 8 (RE1), after week18-19 (if VDC-IE) or week19-20 (if TEMIRI)=RE2, after local treatment ≤week30 (RE3), from week31 (=RE4), 3 years = EOT RE
Percentage of circulating tumour cells in blood and bone marrow to correlate with patient outcome (EFS). Ancillary study
Time Frame: study inclusion, and/or during Procedure=surgery (if done) either after week 19-20=RE2 or after PBSC infusion=RE4
sample collected : primary tumour and metastatic site (if possible)
study inclusion, and/or during Procedure=surgery (if done) either after week 19-20=RE2 or after PBSC infusion=RE4
Percentage of circulating tumour cells in blood and bone marrow to correlate with patient outcome (EFS). Ancillary study
Time Frame: study inclusion, at each evaluation time (RE1=week8 to Response Evaluation before maintenance therapy (RE5=<week38)), every 3 months during 2 years maintenance therapy, at End of Treatment
sample collected : blood
study inclusion, at each evaluation time (RE1=week8 to Response Evaluation before maintenance therapy (RE5=<week38)), every 3 months during 2 years maintenance therapy, at End of Treatment
Percentage of circulating tumour cells in blood and bone marrow to correlate with patient outcome (EFS). Ancillary study
Time Frame: at diagnosis (before treatment), at 1st evaluation time (RE1=wk8 if bone marrow involvement at diagnosis), at RE2=week19-20 (or RE3=<week30), after PBSC infusion=RE4 or RE5=< week38 (if bone marrow involvement at diagnosis), at End of Treatment
sample collected : bone marrow
at diagnosis (before treatment), at 1st evaluation time (RE1=wk8 if bone marrow involvement at diagnosis), at RE2=week19-20 (or RE3=<week30), after PBSC infusion=RE4 or RE5=< week38 (if bone marrow involvement at diagnosis), at End of Treatment
Comparison of transcriptomic profiles between those of primary disease and those of bone marrow metastases to determine if they are the same or not. Ancillary study
Time Frame: study inclusion
Investigation whether the cells from metastatic material harbour a unique transcriptomic signature compared to primary tumour cells : quantification of EWS-ETS transcript and EWS-ETS gene using Polymerase Chain Reaction (PCR) methods to determine the genomic EWS-ETS translocation loci
study inclusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Institut Curie

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
UNICANCER

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Valérie LAURENCE, MD, Institut Curie
  • Principal Investigator: Nadège CORRADINI, MD, Institut d'Hématologie et d'Oncologie Pédiatrique

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 6, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 3, 2017

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 5, 2017

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 21, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 18, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IC 2015-13

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.

IPD Sharing Time Frame

Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.

IPD Sharing Access Criteria

Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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